Traditional Korean Doenjang Restores Splenic and NK Cell Function in Cyclophosphamide-Induced Immunosuppressed Rats

Fermented soybean-based foods contain diverse bioactive compounds with recognized health benefits. Among them, <i>doenjang</i> is widely consumed in East Asia and has been associated with protective effects against several disorders, including immunosuppression. This study evaluated the immunoenhancing effects of <i>doenjang</i> sourced from four regions of Korea in cyclophosphamide (CP)-induced immunosuppressed rats. Four-week <i>doenjang</i> administration restored spleen weight and improved hematological parameters, including white blood cell, lymphocyte, neutrophil, and monocyte counts. Additionally, <i>doenjang</i> intake enhanced immune function, as evidenced by increased splenic natural killer cell activity, increased splenocyte proliferation under lipopolysaccharide- and concanavalin A-stimulated conditions, and higher levels of interleukin (IL)-2, IL-12, interferon-γ, and immunoglobulin G. Furthermore, the suppressed phosphorylation of mitogen-activated protein kinases/nuclear factor kappa B signaling was recovered, accompanied by improved splenic structure. Collectively, our findings demonstrate that the regional varieties of <i>doenjang</i> effectively mitigate CP-induced immune dysfunction, indicating their potential as functional dietary interventions.